AB0412 COMPARISON OF THE EFFICACY AND SAFETY OF A PROPOSED BIOSIMILAR MSB11456 WITH TOCILIZUMAB REFERENCE PRODUCT IN MODERATE-TO-SEVERE RHEUMATOID ARTHRITIS: RESULTS OF A RANDOMIZED DOUBLE-BLIND STUDY
Authors: A. Zubrzycka-Sienkiewicz, M. Misterska-Skora, M. Socik Pojawa, K. Klama, M. Ullmann, C. Petit-Frere, A. Illes, E. Vincent, J. Monnet, J. Brzezicki
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> MSB11456 is a biosimilar to currently marketed originator tocilizumab. It has demonstrated pharmacologic, safety and immunogenic similarity to the US-licensed and EU-approved tocilizumab in healthy subjects. <h3>Objectives</h3> To evaluate the efficacy, immunogenicity and safety of MSB11456 versus EU-approved tocilizumab in patients with moderate to severe rheumatoid arthritis (RA) who had experienced inadequate clinical response to ≥1 disease-modifying antirheumatic drug and were receiving a stable dose of methotrexate. <h3>Methods</h3> Patients were randomised to double-blind subcutaneous injections of 162 mg MSB11456 or EU-approved tocilizumab for 24 weeks (W). At W24, patients receiving EU-approved tocilizumab were re-randomized to continue their treatment or to switch to MSB11456 up to W52. Those receiving MSB11456 continued MSB11456 for the 52W. Primary efficacy endpoint - change from baseline in Disease Activity Score-28 Joint Count (DAS28)-erythrocyte sedimentation rate (ESR) at W24 - was analysed using analysis of covariance to determine the least squares mean (LSM) difference between MSB11456 and EU-approved tocilizumab; MSB11456 was considered equivalent to EU-approved tocilizumab if the 95% confidence interval (CI) for this difference was entirely within the equivalence interval -0.6 to 0.6. Secondary endpoints were 20% improvement in American College of Rheumatology core set measures (ACR20) at W24 and DAS28-ESR at W12. Additional endpoints included ACR50/70, change in DAS28-C-reactive protein (CRP), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) at various time points up to W52, and evaluation of immunogenicity and safety. Results up to W24 are presented. <h3>Results</h3> Clinically relevant LSM decreases from baseline in DAS28-ESR were observed at W24 with MSB11456 and EU-approved tocilizumab (Table 1). As the 95% CI for the LSM difference in the change from baseline in DAS28-ESR between treatments was fully included within the predefined equivalence interval, therapeutic equivalence of MSB11456 and EU-approved tocilizumab was demonstrated. All sensitivity and other efficacy endpoint analyses supported this finding. Immunogenicity results were similar in both treatment groups. Treatment-emergent adverse events (TEAEs) were usually mild or moderate and occurred at similar frequency with both drugs. There were no discernible patterns in terms of the nature, frequency or other characteristics of serious or treatment-related TEAEs to suggest a difference between drugs. <h3>Conclusion</h3> Equivalent efficacy, immunogenicity and safety at W24 of MSB11456 and EU-approved tocilizumab was demonstrated in patients with moderate to severe RA. Pharmacological and clinical similarity of these drugs was supported, therefore MSB11456 can be considered as biosimilar to EU-approved tocilizumab. <h3>Acknowledgements</h3> We thank the patients and the investigators of the working group. <h3>Disclosure of Interests</h3> Anna Zubrzycka-Sienkiewicz: None declared, Maria Misterska-Skora: None declared, Małgorzata Socik Pojawa: None declared, Kamilla Klama: None declared, Martin Ullmann Employee of: Fresenius Kabi SwissBioSim, Corinne Petit-Frere Employee of: Fresenius Kabi SwissBioSim, Andras Illes Employee of: Fresenius Kabi SwissBioSim, Emmanuelle Vincent Employee of: Fresenius Kabi SwissBioSim, Joëlle Monnet Employee of: Fresenius Kabi SwissBioSim, Jan Brzezicki: None declared.